title: The AsaP1 peptidase of Aeromonas salmonicida subsp. achromogenes is a highly conserved deuterolysin metalloprotease (family M35) and a major virulence factor.
abstract: Infections by the bacterium Aeromonas salmonicida subsp. achromogenes cause significant disease in a number of fish species. In this study, we showed that AsaP1, a toxic 19-kDa metallopeptidase produced by A. salmonicida subsp. achromogenes, belongs to the group of extracellular peptidases (Aeromonas type) (MEROPS ID M35.003) of the deuterolysin family of zinc-dependent aspzincin endopeptidases. The structural gene of AsaP1 was sequenced and found to be highly conserved among gram-negative bacteria. An isogenic Delta asaP1 A. salmonicida subsp. achromogenes strain was constructed, and its ability to infect fish was compared with that of the wild-type (wt) strain. The Delta asaP1 strain was found to infect Arctic charr, Atlantic salmon, and Atlantic cod, but its virulence was decreased relative to that of the wt strain. The 50% lethal dose of the AsaP1 mutant was 10-fold higher in charr and 5-fold higher in salmon than that of the wt strain. The pathology induced by the AsaP1-deficient strain was also different from that of the wt strain. Furthermore, the mutant established significant bacterial colonization in all observed organs without any signs of a host response in the infected tissue. AsaP1 is therefore the first member of the M35 family that has been shown to be a bacterial virulence factor.
authors.affiliation: Institute for Experimental Pathology, University of Iceland, Keldur v/Vesturlandsveg, IS-112 Reykjavík, Iceland.
authors.forename: Helga
authors.initials: H
authors.lastname: Arnadottir
authors.forename: Iris
authors.initials: I
authors.lastname: Hvanndal
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Andresdottir
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Burr
authors.forename: Joachim
authors.initials: J
authors.lastname: Frey
authors.forename: Bjarnheidur K
authors.initials: BK
authors.lastname: Gudmundsdottir
mesh_terms: D048409:Aeromonas salmonicida / Q000201:enzymology* / Q000235:genetics* / Q000472:pathogenicity; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D017931:DNA Primers; D005393:Fish Diseases / Q000235:genetics / Q000382:microbiology; D015723:Gene Library; D045726:Metalloproteases / Q000737:chemistry / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics*; D010957:Plasmids; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics*; D020317:Salmo salar / Q000382:microbiology; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics; D018909:src Homology Domains
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D050737:Proto-Oncogene Proteins c-crk; D037521:Virulence Factors; D045726:Metalloproteases; D010447:Peptide Hydrolases